Ammonium Chloride → 7-Bromo-5-fluoroquinoline

HRID 1812246Notes

Reaction equation

HRID 1812246 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5](/[CH:11]=[CH:12]/[CH:13]=O)=[C:4]([F:15])[CH:3]=1.[Cl-].[NH4+]>C(O)C.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]2[C:5]([CH:11]=[CH:12][CH:13]=[N:8]2)=[C:4]([F:15])[CH:3]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 86647069(E)-3-(4-bromo-2-fluoro-6-nitrophenyl)acrylaldehyde

Product 1

HCID 666003857-Bromo-5-fluoroquinolineYield 55.5%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with (E)-3-(4-bromo-2-fluoro-6-nitrophenyl)acrylaldehyde (35 mg, 0.128 mmol), iron powder (0.018 mL, 2.55 mmol, Aldrich) and ammonium chloride (6.83 mg, 0.128 mmol, Aldrich) in ethanol (1 mL). The reaction mixture was stirred and heated in an Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 5 min. The mixture was filtered through a pad of Celite® (diatomaceous earth), washed with EtOAc. The solvent was removed in vacuo and the residue was purified by silica gel chromatography eluting with 20% EtOAc/hexanes to give 7-bromo-5-fluoroquinoline (16 mg, 0.071 mmol, 55.4% yield). 1H NMR (300 MHz, CDCl3) δ 7.20-7.34 (m, 1H) 7.59-7.74 (m, 1H) 7.90 (d, J=8.48 Hz, 1H) 8.58 (d, J=1.61 Hz, 1H) 8.95 (d, J=2.34 Hz, 1H). m/z (ESI, +ve ion) 227.9 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. filtrationThe mixture was filtered through a pad of Celite® (diatomaceous earth)
  3. washwashed with EtOAc
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by silica gel chromatography
  6. washeluting with 20% EtOAc/hexanes

Sources & evidence

ORD record
ord-a21acfe641be434bb47da03342938467
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

Loading…